Resistance Training Protects against Cardiac Damage in Doxorubicin-Induced Cardiotoxicity in Rats.

PURPOSE

Doxorubicin (DOX) is an effective chemotherapeutic agent that leads to a dose-dependent cardiotoxicity that may ultimately result in heart failure. This study explores whether resistance training (RT) may mitigate DOX-induced cardiac damage and examines the expression of proteins involved in muscle anabolism, catabolism, and mitochondrial dynamics in the left ventricle.

METHODS

Male Sprague Dawley rats (3 months old) were divided into control (saline/sedentary, n = 10), Dox/Sed (DOX/sedentary; initial n = 16), and Dox/Tr (DOX/RT; initial n = 16) groups. DOX or saline was administered for ten consecutive days (1 mg/kg/d; i.p.), starting concomitantly with RT, that consisted of ladder climbing with tail-attached weights (15 reps/day; 5 d/wk; 20-60% of maximal load; for eight weeks). 72 h after the last RT session, rats were euthanized and left ventricle fragments were dissected and processed for microscopy and Western blot.

RESULTS

RT reduced the early and high mortality observed in Dox/Sed group and prevented DOX-induced cardiac fiber atrophy and fibrosis. Cardiomyocytes ultrastructural damage, including misaligned sarcomeres, myofibril rupture, autophagosome presence, and mitochondrial damage, was mitigated by RT. While Akt, p-Akt, MuRF1, and Atrogin-1 levels in left ventricle were similar among groups, both DOX groups displayed reduced mTOR, ERK, and p-ERK expression compared to control group. Regarding proteins related to mitochondrial dynamics, OPA1 expression did not differ among groups, Mfn2 was significantly lower in both DOX groups compared to control, and FIS1 levels were lower only in Dox/Tr group. In addition, Dox/Tr presented higher levels of PGC1α expression in comparison with control and Dox/Sed groups.

CONCLUSIONS

RT may be valuable to protect the heart against the structural damage induced by DOX via the modulation of proteins involved in mitochondrial dynamics.